Despite evidence probiotics can ameliorate gastrointestinal inflammation and modulate immune defenses at mucosal surfaces, virtually nothing is known of their potential to impact transmission of HIV-1 in pediatric populations. In Sub-Saharan Africa, the rate of new HIV-1 infections among children exceeded 700,000 in 2004; from one-third to one-half of these infections were acquired by breastfeeding. Epidemiologic studies indicate that infants ingesting both HIV-infected breast milk and supplemental foods or fluids are at significantly higher risk of HIV-1 transmission compared to their exclusively breastfed counterparts. While the underlying mechanism(s) for this are unknown, it is presumed that induction of inflammatory responses in the newborn gut following exposure to foreign food antigens or enteric pathogens increases mucosal permeability, thereby facilitating HIV-1 penetration and replication. The proposed project will determine the feasibility of conducting a randomized, double-blinded controlled study of the probiotic Lactobacillus GG (LGG) as a dietary intervention to reduce gastrointestinal inflammation in infants exposed to HIV-1 through breastfeeding and mixed-feeding practices. This study will be conducted in Dar es Salaam, Tanzania in collaboration with Muhimbili University College of Health Sciences. We will test the hypothesis that oral administration of LGG-supplemented porridge to HIV-exposed, breastfeeding infants reduces intestinal mucosal inflammation and has the potential decrease the risk of HIV-1 transmission. We will address this hypothesis through two specific aims: the first to determine the feasibility of administering LGG in a traditional maize porridge to infants randomized to this intervention, and the second to determine the effectiveness of LGG-supplemented porridge in reducing gastrointestinal inflammation and colonization with enteric pathogens. The primary outcome of the study is a reduction in the levels of two fecal biomarkers for intestinal inflammation, TNF-alpha and calprotectin. Secondary outcomes are the ability to collect supportive data on infant feeding practices and exposure to enteropathogens, and to assess maternal HIV-1 viral load and infant HIV-1 status. Taken together, these data will be used to guide the development of a large-scale clinical trial of LGG in HIV-exposed, breastfeeding infants to determine the efficacy of this intervention in reducing HIV-1 mother-to-child transmission. If effective, probiotic intervention with LGG has the potential to significantly reduce infant deaths due to infection with HIV-1 and other infectious enteric pathogens. Utilizing a traditional food for probiotic delivery provides an intervention that is affordable, culturally accepted and readily renewable, and would be amenable for use in resource-constrained countries in Sub-Saharan Africa. [unreadable] [unreadable] [unreadable]